This project will pursue the study of cellular and tissue mechanisms in the remodelling of the structure of the lungs. The plan involves progress simultaneously on each of several fronts. Recent advances in experimental emphysema suggest that pulmonary elastic tissue plays a major role in the maintenance of normal lung architecture. Thus, biochemical efforts will be directed mainly toward an improved description and understanding of elastin. Connective tissue elements will also be studied by conventional histological techniques, and by electron microscopy during human diseases and with experimental emphysema. Degradative enzymes for connective tissues are of special importance in this program. Efforts will be directed at isolation and purification of the collagenases that have already been identified in alveolar macrophages and in the media obtained during the culture of lung tissue in vitro. Similarly, elastase will be sought, identified and characterized from macrophages and from lung tissue cultures. The study of naturally-occurring inhibitors will be important with each degradative enzyme. The availability of a large number of odd antitrypsin phenotypes will facilitate these studies with alpha-l antitrypsin. The urinary excretion of elastin breakdown products might prove of interest in several disorders that involve the lung and other organs.